In acute pancreatitis, initiating cellular events causing acinar cell injury includes co-localization of zymogens with lysosomal hydrolases, leading to premature enzyme activation and pathological exocytosis of zymogens into the interstitial space. This is followed by processes that accentuate cell injury; triggering acute inflammatory mediators, intensifying oxidative stress, compromising the microcirculation and activating a neurogenic feedback. Such localized events then progress to a systemic inflammatory response leading to multiorgan dysfunction syndrome with resulting high morbidity and mortality. The present review discusses some of the most recent insights into each of these cellular processes postulated to cause or propagate the process of acute pancreatitis, and also the role of alcohol and genetics.